The effect of grapefruit juice on drug disposition

INTRODUCTION: Since their initial discovery in 1989, grapefruit juice (GFJ)-drug interactions have received extensive interest from the scientific, medical, regulatory and lay communities. Although knowledge regarding the effects of GFJ on drug disposition continues to expand, the list of drugs studied in the clinical setting remains relatively limited. AREAS COVERED: This article reviews the in vitro effects of GFJ and its constituents on the activity of CYP enzymes, organic anion-transporting polypeptides (OATPs), P-glycoprotein, esterases and sulfotransferases. The translational applicability of the in vitro findings to the clinical setting is discussed for each drug metabolizing enzyme and transporter. Reported AUC ratios for available GFJ-drug interaction studies are also provided. Relevant investigations were identified by searching the PubMed electronic database from 1989 to 2010. EXPERT OPINION: GFJ increases the bioavailability of some orally administered drugs that are metabolized by CYP3A and normally undergo extensive presystemic extraction. In addition, GFJ can decrease the oral absorption of a few drugs that rely on OATPs in the gastrointestinal tract for their uptake. The number of drugs shown to interact with GFJ in vitro is far greater than the number of clinically relevant GFJ-drug interactions. For the majority of patients, complete avoidance of GFJ is unwarranted.